Diffuse astrocytoma of the brain

According to the World Health Organization classification, diffuse astrocytoma of the brain belongs to the II degree of malignancy of tumor processes - primary brain neoplasms. The prefix "diffuse" denotes the absence of a distinguishable border between pathologically altered and healthy brain tissue. Previously, diffuse astrocytoma was called fibrillary.

The degree of malignancy of the pathology is low. Treatment is mainly surgical. [1]

Epidemiology

Diffuse cerebral astrocytoma of low malignancy is more often found in patients aged 20 to 45 years. The average age of the patients is 35 years.

Specialists talk about two peaks in the incidence of the disease over the course of a lifetime. The first peak is during childhood - from six to twelve years of age, and the second peak is from about 26 to 46 years of age.

Pediatric diffuse astrocytomas more often affect the brain stem. The disease is diagnosed in more cases in men, and women are diagnosed less often.

And some more stats:

• Approximately 10% of patients die before a brain astrocytoma is diagnosed;
• In 15% of cases, patients cannot tolerate complex therapy;
• about 9% refuse treatment;
• 12-14% of cases are treated with surgery or radiation therapy alone.

Causes of the diffuse cerebral astrocytoma.

Scientists cannot give a clear cause of diffuse astrocytoma of the brain. Presumably, the tumor has a multifactorial origin - that is, it develops as a result of sequential or simultaneous exposure to a number of adverse factors.

Observers point to an increased propensity to the disease in people living in large cities with developed industrial and transportation infrastructure. According to some reports, the negative impact is caused by:

• inhaling exhaust fumes;
• ultraviolet irradiation;
• contact with household chemicals;
• general or localized radiation exposure.

The occurrence of diffuse astrocytoma is also promoted by improper nutrition of most people. Carcinogens, chemical components (flavor enhancers, flavorings, dyes, etc.), trans fats have their negative effect: it is often poor quality food that provokes primary pathological intracellular changes.

However, all of the above reasons are only possible links in the chain of pathology development. It is almost impossible to know the exact origin of diffuse astrocytoma: for this purpose, it is necessary to analyze in detail the history of life and disease, trace the slightest changes in the patient's state of health from the moment of birth, determine the specifics of nutrition, etc. [2]

Risk factors

Both the causes and possible risk factors for diffuse astrocytoma have not been fully elucidated to date. However, studies have demonstrated that the disease is found more often in some people. For example:

• men get astrocytoma more often than women;
• Diffuse astrocytomas are more likely to be diagnosed in whites;
• In some cases, hereditary history is also relevant.

Tumors in the brain can also be associated with factors such as:

• Radiation exposure (according to studies, the risks of pathology are higher in workers in the nuclear industry).
• Exposure to formalin (formaldehyde, occupational poisoning).
• Effects of vinyl chloride (used in plastic production, occupational poisoning).
• Effects of acrylonitrite (used in plastic and textile manufacturing, occupational intoxication).

According to experts, head injuries and cell phone use do not become causes for the development of diffuse astrocytoma of the brain.

Pathogenesis

Diffuse astrocytoma refers to glial neoplasms that develop from astrocytic cells, which are supporting cells for neurons. With the help of astrocytes, new associative complexes are provided, but under certain negative conditions, such cells massively accumulate, as a result of which the tumor appears.

Diffuse astrocytoma is the most common neuroectodermal tumor characterized by predominantly slow growth. Although in some cases, the pathological focus still reaches a large size and begins to squeeze nearby brain structures. Clear configurations of the neoplasm are indistinguishable.

The exact pathogenetic mechanisms of pathology development have not been investigated. It is known that diffuse astrocytoma is formed in the white matter of the brain, usually has medium size and blurred borders. It is amenable to surgical treatment, supplemented by chemotherapy and radiation therapy. In some cases, it grows to giant size, sprouting into neighboring tissues. Transformation of a low malignant astrocytoma into a high malignant one is likely.

Symptoms of the diffuse cerebral astrocytoma.

Diffuse astrocytoma of the brain does not always manifest in the same way. There may be a combination of local, general symptoms. Often tumor growth becomes the cause of increased intracranial pressure, compression of intracerebral structures, marked intoxication.

The most common first signs of pathology:

• severe head pain, prolonged or constant;
• visual double vision;
• loss of appetite;
• nausea to the point of vomiting;
• general and severe weakness;
• cognitive decline;
• memory loss, inattention.

The overall symptom intensity depends largely on the location and size of the diffuse astrocytoma, as can be seen in the following table.

Astrocytoma of the cerebellum	The first sign is impaired motor coordination. Mental disorders, neuroses, sleep disorders, aggressive behavior are possible. As brain structures are compressed, metabolic changes, focal symptoms are observed - in particular, muscle weakness, paresthesias.
Astrocytoma of the temporal lobe	There is a noticeable deterioration of speech, reduced ability to information reproduction, weakening of memory. Gustatory and auditory hallucinations are possible.
Astrocytoma between the occipital and temporal lobes	There are visual disorders, double images, the appearance of a foggy shroud before the eyes. There may be deterioration of fine motor skills.

In some cases, the symptomatology appears gradually, so it is difficult to distinguish the manifestations. In aggressive course, the clinical picture immediately becomes pronounced and develops rapidly.

Forms

Astrocytomas are classified according to their microscopic characteristics. The more pronounced the changes in cellular structures, the higher the degree of malignancy.

Diffuse astrocytoma grade 1 is considered the least malignant, and its tumor cells have similarities to normal structures. The tumor develops very slowly and is more common in childhood and adolescence.

Diffuse astrocytoma grade 2 also refers to low malignant tumors, which are characterized by slow growth. The tumor is more often found in patients between 30 and 40 years of age.

Diffuse astrocytoma of grade 3 and higher is always more malignant than the initial degrees of pathology. It is characterized by aggressiveness and a faster rate of development, with probable spread to all brain structures.

The third and fourth degrees of diffuse astrocytoma are found, as a rule, in patients 40-60 years old. The prognosis of such pathologies is disappointing.

Diffuse cerebral astrocytoma is a term that is not collectively categorized as a noninfiltrative astrocytoma. Thus, pleomorphic, piloid, and subependymal giant cell astrocytomas are distinct pathologies with their own characteristics and treatment tactics.

Directly, diffuse astrocytoma is subdivided into two molecular lineages, which corresponds to IDH status:

1. IDH mutant series.
2. IDH Wild Row.

If the status of the neoplasm is uncertain, it is said to be a diffuse astrocytoma NOS (Not Otherwise Specified).

It must be understood that the IDH marker must contain mutations and define the 1p19q status without codelination. New neoplasms with 1p19q codelation are currently referred to as oligodendrogliomas. [3]

Complications and consequences

The probability of adverse effects in diffuse astrocytoma is quite high. The growing tumor process is prone to recurrence, including in the first years after surgical removal of the neoplasm. Timely detected and successfully operated astrocytomas are less likely to recur.

Untimely recognized pathology can lead to a gradual increase in intracranial pressure, which, in turn, will cause nausea and vomiting attacks, headaches. Over time, patients have impaired vision (up to complete loss of visual function), speech, hearing, memory deterioration.

Initially low malignant disease can be transformed into a high malignant disease. Treatment of such pathology will be much more difficult, and the prognosis will be worse.

In some patients, the possibility of partial or complete paralysis cannot be ruled out. In order to prevent complications, it is very important to detect the tumor before it becomes life-threatening. [4]

Diagnostics of the diffuse cerebral astrocytoma.

A general examination, gathering information about symptoms, the patient's general health, and past illnesses allow the presence of diffuse astrocytoma of the brain to be suspected. Within the framework of neurological diagnostics, the doctor evaluates such aspects of brain function as memory, hearing and vision, muscular capabilities, vestibular, coordination and reflex activity.

During an ophthalmologic examination, the doctor evaluates the quality of visual function, measures intraocular pressure.

Instrumental diagnostics is used directly to detect diffuse astrocytoma, determine its size and degree of lesion:

• MRI - magnetic resonance imaging is a basic imaging method that provides complete information about the type of tumor process and its extent. In addition, MRI is performed after surgical intervention to assess its quality.
• CT - A CT scan helps to obtain a cross-sectional view of brain structures. The procedure involves the use of X-rays. The method allows you to identify even small tumors.

Among additional diagnostic studies, electroencephalography, angiography, ophthalmoscopy, and histological examination of the tumor are leading. [5]

Blood tests are represented by the following investigations:

• General blood test with determination of the number of erythrocytes, platelets, leukocytes.
• Blood Biochemistry.
• Oncomarkers.

With diffuse astrocytoma, the circulatory system is significantly affected, the hemoglobin level decreases. Intoxication negatively affects erythrocyte membranes, anemia worsens. [6]

Urinalysis is usually unremarkable.

Differential diagnosis

Differential diagnosis is made with such pathologies:

• ischemic stroke of the brain;
• acute disseminated encephalomyelitis, herpetic encephalitis (encephalitis, cerebritis);
• anaplastic astrocytoma;
• cortical neoplasms, angiocentric glioma, oligodendroglioma.

Diffuse astrocytoma of the spinal cord is detected during CT or MRI: the localization and size of the tumor focus are specified, the condition of nearby tissues and structures is assessed. The degree of malignancy is determined by histologic analysis. Pathologically altered tissues are removed during stereotactic biopsy, after which they are carefully studied in the laboratory and a medical report is issued.

Treatment of the diffuse cerebral astrocytoma.

Treatment of patients with diffuse cerebral astrocytoma is always urgent and complex. The key therapeutic modalities are usually as follows:

• surgical procedure;
• radiotherapy;
• chemotherapy;
• Targeted therapy and their combination.

Chemotherapy involves taking the drugs internally or injecting them intravenously. The goal of this treatment is the complete destruction of malignant cells. The drug component enters the circulatory system and is transported to all organs and tissues. Unfortunately, the effects of drugs are also reflected in healthy cells, which is accompanied by intense side symptoms.

Targeted (or molecularly targeted) therapy is a treatment with specific drugs that can block the growth and spread of malignant cells by affecting individual molecular links involved in tumor development. In contrast to chemotherapy, targeting agents affect only pathologically altered structures, so they are safer for healthy organs.

Radiation treatment is prescribed before and after surgery. In the first case, it is used to reduce the size of the astrocytoma, and in the second case, to prevent the possibility of recurrence.

Radiotherapy helps to reduce the size of the neoplasm. The method can be presented:

• stereotactic radiotherapy and radiosurgery (a session or course of therapy is possible);
• Brachytherapy (limited internal irradiation of pathologic tissue);
• craniospinal radiotherapy (radiation to the spinal cord).

However, surgery is considered the main treatment option for diffuse astrocytoma.

Medications

Temozolamide when taken orally is rapidly absorbed, undergoes spontaneous hydrolysis in the circulatory system, is transformed into an active metabolic substance capable of penetrating the blood-brain barrier. The drug has antiproliferative activity.

Avastin is no less effective, providing clear clinical benefits and eliminating cerebral edema, reducing the need for corticosteroids, optimizing radiological response in 30% of patients. In addition, Avastin reduces vascular permeability, eliminates peritumoral edema, reduces the severity of neurological symptoms.

Targeted drugs that selectively block VEGF are considered to be the most promising in terms of treatment. Erlotinib, Gefitinib (EGFR inhibitors), Bevacizumab (Avastin, VEGF inhibitor) are currently the most available drugs.

Dosages and duration of treatment with the drugs are individualized. For example, Avastin can be prescribed at the rate of 7 to 12 mg/kg of weight, which is about 800 mg per course on average. The number of such courses varies from 4 to 8 with three-week intervals between them. The drug can be combined with adjuvant chemotherapy with Temozolomide.

Dermatologic adverse reactions may include acne, dry skin and itching, photosensitivity, hyperpigmentation, hair loss and changes in hair structure.

Lapatinib, Imatinib may be used. Symptomatic drugs are prescribed to relieve the general condition, reduce the symptoms of diffuse astrocytoma and level the side effects of chemotherapy:

• Analgesics (including opioids);
• antiemetics (Cerucal);
• tranquilizers, nootropics;
• anticonvulsants;
• Hormonal (corticosteroid) medications.

The effectiveness of treatment is largely determined by its timeliness and competence. If diffuse astrocytoma of the brain is diagnosed in time, then often even conservative therapy can give a good result: the patient is cured and lives a full life. [7]

Surgical treatment

Depending on the extent of the tumor process and its spread, surgery is performed:

• in the form of a complete resection of the astrocytoma;
• in the form of partial removal of the most accessible pathologic tissues (to relieve the patient's condition and reduce intracranial pressure).

In addition to direct treatment, surgery is also necessary to perform a biopsy - the removal of biomaterial for subsequent histologic examination.

Choosing a method of surgical intervention, the doctor is guided by the availability of the tumor focus, physical condition and age of the patient, assesses all the risks and likely complications of surgery.

Before surgery, the patient is injected with a special fluorescent substance. This enhances visualization of the fuzzy diffuse astrocytoma and reduces the risk of damage to nearby structures.

Most patients undergo general anesthesia during surgery. The exception is astrocytomas localized near functional areas responsible for speech and visual abilities. During such intervention, the patient is talked to, his perception is controlled.

Resection of diffuse astrocytoma of the brain is most often performed in one of two ways:

• endoscopic cranial trepanation (minimally invasive intervention with tumor removal using endoscopic equipment through small holes);
• open intervention with removal of a cranial bone element (microsurgical operation with the use of navigation equipment, unlike endoscopic trepanation, is longer and more complex).

After surgical treatment, the patient is transferred to the intensive care unit. About 4-5 days later, a CT or MRI control study is performed.

The full rehabilitation period after removal of diffuse astrocytoma can be about three months. The rehabilitation scheme is prepared by a doctor individually and usually includes physical therapy, manual therapy, psycho-logopedic help, etc.

Prevention

Primary preventive measures should be aimed at eliminating unfavorable influences that may cause the development of diffuse astrocytoma. First of all, it is necessary to completely eliminate or significantly reduce the influence of carcinogens. Thus, it is important to pay attention to such factors:

• nutrition;
• bad habits (smoking, alcoholism, drug addiction, substance abuse);
• infections (particularly viral infections);
• sedentary lifestyle;
• polluted environment;
• irradiating factors (ultraviolet rays, ionizing radiation, etc.).

Patients with a history of cancer should see a doctor regularly for diagnostic measures.

Regular preventive check-ups and examinations according to age or risk group help to prevent the appearance of diffuse astrocytoma of the brain, or detect the pathology at an early stage of its development, which will allow to perform successful organ-preserving specific treatment.

In order to prevent recurrences of astrocytoma after comprehensive treatment, patients are registered for life in an oncological institution, where they regularly perform the necessary diagnostics prescribed by doctors.

Forecast

The chances of curing patients from diffuse astrocytoma are always different and depend on the specific neoplasm, its location, and size. If the patient underwent successful surgical intervention, the survival rate may be 90 percent or more (in case of a highly malignant tumor - about 20 percent). [8]

Prognostic information can be altered by factors such as:

• The degree of malignancy of the astrocytoma (low malignant tumors grow slowly and are less prone to recurrence, while high malignant tumors respond poorly to treatment and may recur).
• Localization of the tumor focus (the prognosis is more comforting for neoplasms with localization in the cerebral hemispheres or cerebellum).
• Accessibility of the tumor (only a nidus that is in an instrument-accessible location can be removed completely without residue).
• Age of the patient at the time of diagnosis of diffuse astrocytoma (in young children younger than three years of age, the outcome of treatment of low malignant astrocytoma is less favorable, and high malignant - on the contrary, more favorable).
• Prevalence of the cancer process (astrocytoma with metastases is worse to treat).
• Tumor recurrence is worse to treat than the primary process.

Even if diffuse astrocytoma of the brain has been successfully treated, the patient should continue to undergo routine examinations and diagnostic procedures to monitor the possible recurrence or change in the dynamics of the pathology. Depending on the therapeutic response, the type of neoplasm, and the individual characteristics of the patient, the attending physician draws up a scheme of regular examinations.